Starting Dose of Nortriptyline
The recommended starting dose of nortriptyline is 10 mg at bedtime for elderly patients and 25 mg three to four times daily (or as a single bedtime dose) for younger adults, with the FDA label specifying that dosage should begin at a low level and be increased gradually as required. 1, 2
Standard Adult Dosing
- For general adult patients, the FDA-approved starting regimen is 25 mg given 3 or 4 times daily, though the total daily dose may alternatively be given once daily at bedtime 2
- The initial dose should be started low and titrated upward based on clinical response and tolerability, checking carefully for evidence of intolerance 2
- As an alternative approach for outpatients, starting with 25 mg at bedtime and titrating upward is common in clinical practice 3
Elderly and Frail Patients
- For elderly patients, the starting dose should be 10 mg at bedtime, which is significantly lower than the standard adult dose due to increased sensitivity to side effects 1, 4
- The FDA label specifically recommends 30 to 50 mg/day in divided doses for elderly patients as the usual maintenance range, but initiation should start lower 2
- Guidelines emphasize starting at 10 mg/day in older patients to minimize anticholinergic effects, cardiotoxicity, and orthostatic hypotension 1
Titration Strategy
- Increase the dose gradually using increments of the initial dose every 5 to 7 days until therapeutic benefits or significant side effects become apparent 1
- The therapeutic target plasma level "window" is 50 to 150 ng/mL (190 to 570 nmol per L), which helps guide dose adjustments 1
- When doses above 100 mg daily are administered, plasma levels should be monitored and maintained in the optimum range of 50 to 150 ng/mL 2
Maximum Dosing and Safety Limits
- Doses above 150 mg per day are not recommended per FDA labeling 2
- Doses greater than 100 mg/day are associated with increased risk of sudden cardiac death, particularly in patients with cardiovascular disease, requiring extreme caution 1, 4
- A baseline ECG is essential before initiating treatment; if the PR or QTc interval is prolonged, nortriptyline should not be used 1, 4
Clinical Considerations
- Nortriptyline tends to be more sedating than other tricyclics like desipramine, making it useful for patients with agitated depression and insomnia when dosed at bedtime 1
- It has fewer anticholinergic effects compared to amitriptyline, making it the preferred tricyclic for elderly patients 4
- A full therapeutic trial requires at least 4 to 8 weeks to assess efficacy 1
- Common side effects include dry mouth, constipation, blurred vision, somnolence, and potential cardiac effects such as QTc prolongation 4
Special Populations
- For smoking cessation trials, nortriptyline was started at 25 mg before bed 10 days prior to quit day and titrated to 75 mg/day or the maximal tolerated dose 3
- In frail elderly patients (average age 84), the average dose required to achieve a plasma level of 100 ng/mL is approximately 80 mg/day, though individual requirements vary by a factor of 20 5
- A 25-mg test dose can be used in elderly patients to predict steady-state levels and individualize dosing, avoiding the higher 50-mg test dose that may cause unmanageable acute side effects 6, 7